tbuckley/cabot-search huggingface dataset:
Abstract PD12-07: PD12-07 The effect of BMI on the pathological response after neoadjuvant systemic therapy in breast cancer patients: a nationwide retrospective study
Authors: Britt Jansen, Anke Gielen, Mariette Agteroff, Marissa van Maaren, Sandra Beijer, Martine Moossdorff, Marjolein Smidt, Emily Postma
Journal: Cancer Research (2023)

Abstract Background: Neoadjuvant systemic therapy is increasingly applied in breast cancer patients to improve surgical and oncological outcomes. There is only limited data from clinical practice on the relevance of body mass index (BMI) on the pathologic complete response (pCR) rate following neoadjuvant systemic treatment (NST). We aimed to retrospectively analyze the impact of BMI on pCR after NST for Dutch breast cancer patients. Methods: Patients diagnosed with invasive breast cancer between 2019 and 2021 who were treated with NST followed by a surgical procedure, were selected from the Netherlands Cancer Registry (NCR). Patients were divided into three groups based on BMI: patients with underweight/normal weight (BMI&amp;lt; 25 kg/m2), patients with overweight (BMI 25-29.9 kg/m2) and patients with obesity (BMI&amp;gt;30 kg/m2). Patients with unknown BMI, ER/PR/HER2 or pCR status were excluded for analysis. The primary outcome was pCR after NST. The association between BMI and pCR was estimated using logistic regression models with the expression of odds ratios (ORs). Results: After applying in- and exclusion criteria, 4430 patients were included for analysis, statified into four molecular breast cancer subtypes; HR+/HER2- (n=2256), HR+/HER2- (n=722), HR-/HER2+ (n=405) and HR-/HER2- (n=1047). The predictors age, differentiation grade, histological type, clinical tumor (cT) and nodal (cN) stage and molecular breast cancer subtype were found siginificant for achieving pCR after NST. Multivariabele regression analysis identified differentiation grade, cT and cN stage and molecular subtype as independent predictors for pCR after NST. There was no association between pCR and (continuous or categorical) BMI. Above mentioned analyses performed by stratification according to molecular breast cancer subtype, also showed no statistically meaningful association between BMI and pCR. Conclusion: In this nationwide retrospective cohort study, evaluating 3340 patients with invasive breast cancer, we found no evidence of BMI being a predictive factor for achieving pCR following NST in neither the whole cohort, nor stratified according to molecular breast cancer subtype. Table 1. Multivariable regression analysis of the total cohort Citation Format: Britt Jansen, Anke Gielen, Mariette Agteroff, Marissa van Maaren, Sandra Beijer, Martine Moossdorff, Marjolein Smidt, Emily Postma. PD12-07 The effect of BMI on the pathological response after neoadjuvant systemic therapy in breast cancer patients: a nationwide retrospective study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD12-07.
Abstract P3-10-02: Cell cycle dysregulation in breast cancer: why the details matter
Authors: Sinem Seker, Elena Oropeza, Sabrina Carrel, Aloran Mazumder, Nindo Punturi, Jonathan Lei, Meenakshi Anurag, Bora Lim, Matthew Bainbridge, Svasti Haricharan
Journal: Cancer Research (2023)

Abstract Cell cycle dysregulation is a prerequisite for cancer formation. However, whether the type of cell cycle dysregulation event a cell incurs during transformation to malignancy influences the type of cancer that evolves or clinical outcome is unknown. In a comprehensive analysis of cell cycle dysregulation in breast cancer patient tumors, we associate mutations in each of four cell cycle checkpoint kinase genes, ATM, CHEK2, ATR and CHEK1, with known tumor characteristics and clinical outcome, and test these associations experimentally using transgenic mice, patient-derived xenografts and breast cancer cell line model systems. Results of this work demonstrate that dysregulation of specific cell cycle checkpoint kinases differently impacts the type of breast cancer that evolves in patients and in experimental model systems, and influences treatment responsiveness and disease progression. For instance, CHEK2 mutations associate preferentially with the incidence of metastatic, premenopausal estrogen receptor (ER)+/HER2- breast cancer in patient data (p=0.001) that is resistant to standard frontline therapy (HR=6.15, p=0.01). These associations appear causal when tested in an immune-competent genetically-engineered mouse model of Chk2 loss, in patient-derived xenograft, and in cell line experiments. On the other hand, ATR mutation by itself is not frequent in ER+/HER2- breast cancer, but co-incident mutation of ATR and TP53 is 2-fold enriched (p=0.002) and associates with metastatic progression (HR=2.01, p=0.007). Concordantly, ATR dysregulation induces metastatic phenotypes in ER+/HER- TP53 mutant, but not in TP53 wildtype, cell lines. Together, these results systematize the impact of individual cell cycle checkpoint kinases on the evolution of cancer subtypes, and on disease progression. Statement of Significance These findings reframe the paradigm of breast cancer classification through the lens of early cell cycle dysregulation events by demonstrating that cell cycle decisions during malignant transformation can direct the type of breast cancer that evolves, how it will respond to treatment, and whether it will metastasize. This work provides rationale for streamlined testing of checkpoint kinase dysregulation to improve precision diagnostics for cancer patients. Citation Format: Sinem Seker, Elena Oropeza, Sabrina Carrel, Aloran Mazumder, Nindo Punturi, Jonathan Lei, Meenakshi Anurag, Bora Lim, Matthew Bainbridge, Svasti Haricharan. Cell cycle dysregulation in breast cancer: why the details matter [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-10-02.
Abstract P4-02-23: Integrating tumor-intrinsic and immunological factors to improve locoregional treatment individualization of high-risk breast tumors
Authors: Axel Stenmark Tullberg, Martin Sjöström, Emma Niméus, Fredrika Killander, Dan Lundstedt, Anikó Kovács, Erik Holmberg, Per Karlsson
Journal: Cancer Research (2023)

Abstract Background: The influence of the local immune infiltrate on tumor progression is dependent on tumor-intrinsic characteristics. Among highly aggressive subtypes, an immune infiltrate is associated with a favorable prognostic effect. The aim was to investigate whether the integration of histological grade and degree of tumor-infiltrating lymphocytes (TILs) permits improved treatment individualization for clinically high-risk tumors. Methods: The SweBCG91RT trial included 1178 patients with stage I-IIA breast cancer, randomized to breast-conserving surgery with or without adjuvant RT, and followed for a median time of 15.2 years. In total, 8% were treated with systemic therapy. Histological grade and TILs were evaluated on whole-tissue sections by board-certified pathologists. Grade III tumors were compared to grade I and II tumors. TILs were classified as high (&amp;gt;=10%) or low (&amp;lt; 10%). The primary endpoint was ipsilateral breast tumor recurrence (IBTR) within 10 years. Results: In total, 134 (57%) of the 235 grade III tumors had high TIL levels compared to grade I/II tumors where 142 (19.7%) out of 721 tumors exhibited high TIL levels. Grade III tumors with high TILs had a reduced risk of IBTR (HR 0.49, CI 95% 0.26-0.91, p=0.025) compared to grade III tumors with low TILs (HR 1.0). Among grade I/II tumors, high TILs was not prognostic (HR 1.02, CI 95% 0.62-1.68, p=0.95) compared to grade I/II tumors with low TILs (HR 1.0). Grade III tumors with low TILs had a high risk of recurrence without RT (36.2%) and derived benefit from RT (HR 0.16, CI 95% 0.047-0.53, p=0.0029). In contrast, grade III tumors with high TILs had a lower risk of IBTR without RT (14.5%) and did not benefit significantly from RT (HR 0.71, CI 95% 0.26-1.90, p=0.50). Conclusion: Measurements of the local immune infiltrate may improve treatment individualization when integrated with tumor-intrinsic features of aggressivity, such as histological grade. High-risk tumors with an immune infiltrate may be candidates for RT de-escalation. Citation Format: Axel Stenmark Tullberg, Martin Sjöström, Emma Niméus, Fredrika Killander, Dan Lundstedt, Anikó Kovács, Erik Holmberg, Per Karlsson. Integrating tumor-intrinsic and immunological factors to improve locoregional treatment individualization of high-risk breast tumors [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-02-23.
Abstract PD3-06: Robotic Stereotactic APBI for Early-Stage Breast Cancer: 2-year Outcomes of a Prospective Multi-Institutional Trial
Authors: Jonathan M. Cantalino, David D’Ambrosio, Arica Hirsch, Brian Collins, Malika Danner, Dawn Matsanka, Sonali Rudra, Simeng Suy, Sean Collins, Monica Pernia Marin, Michael Good, Jing Feng, John Lamond, Deborah Markiewicz, Rachelle Lanciano, Olusola Obayomi-Davies
Journal: Cancer Research (2023)

Abstract Purpose: Outcomes following adjuvant accelerated partial breast irradiation (APBI) in select women with early-stage breast cancer are comparable to whole breast irradiation. Robotic stereotactic accelerated partial breast irradiation (RSAPBI) with fiducial tracking is an attractive treatment option, but limited outcomes data are available for this approach. We report 2-year outcomes for a prospective multi-institutional trial treating select women with RSAPBI. Materials and Methods: Post-menopausal women with DCIS and Stage IA breast cancer were treated over a five-year period extending from November 2015 to November 2020 and were followed for a minimum of 18 months. Treatments were delivered with a robotic radiosurgery system. Four gold fiducials were implanted around the lumpectomy cavity prior to the start of treatment for tumor bed delineation and target tracking. The CTV was defined as the lumpectomy cavity with a uniform 5-15 mm expansion confined to the breast tissue and the PTV was defined as the CTV with a 0-5 mm uniform expansion. The PTV was prescribed 30 Gy in 5 fractions. Disease status assessments were completed at 4 weeks, 3 months, 6 months, 12 months, 18 months, 24 months and yearly intervals thereafter for five years. Results: Eighty-one patients (median age 68 years) with hormone receptor-positive tumors were treated over a median 9 days (range, 5-15). Sixty-eight women had invasive ductal carcinoma (84%) and thirteen had DCIS (16%). The median treated PTV was 108 cm3 (IQR 66-156) and the median prescription isodose line was 81% (IQR 79-83). The median CTV expansion was 10 mm (range 5-10) and the median PTV expansion was 3 mm (range 0-5). At a median follow up of 2 years there was one new ipsilateral breast tumor diagnosed. There were no local, regional, or distant treatment failures. Conclusions: Two-year results suggest that RSAPBI with fiducial tracking is an effective technique for the adjuvant treatment of post-menopausal women with hormone receptor-positive early-stage breast cancer. Additional follow-up is planned to confirm this preliminary finding. Citation Format: Jonathan M. Cantalino, David D’Ambrosio, Arica Hirsch, Brian Collins, Malika Danner, Dawn Matsanka, Sonali Rudra, Simeng Suy, Sean Collins, Monica Pernia Marin, Michael Good, Jing Feng, John Lamond, Deborah Markiewicz, Rachelle Lanciano, Olusola Obayomi-Davies. Robotic Stereotactic APBI for Early-Stage Breast Cancer: 2-year Outcomes of a Prospective Multi-Institutional Trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD3-06.
Abstract PD2-07: Tumor CD73 regulates zoledronate induced TIL accumulation into triple negative breast cancer
Authors: Nataliia Petruk, Arafat Siddiqui, Sina Tadayon, Arja Jukkola, Jorma Määttä, Pieta Mattila, Jouko Sandholm, Katri S. Selander
Journal: Cancer Research (2023)

Abstract Background: CD73 is a membrane-bound protein that by extracellular adenosine production, regulates immune cell function. Low CD73 expression is associated with better prognosis among triple-negative breast cancer (TNBC) patients. Adjuvant bisphosphonates (BPs, such as zoledronate) improve survival among post-menopausal breast cancer patients, but the mechanism for this is unknown. Since BPs also affect immune cells, we studied 1) whether zoledronate-treatment has an effect on tumor infiltrating lymphocytes (TILs) and 2) whether tumor CD73 expression affects these responses in TNBC tumors. Methods: 4T1 mouse mammary cells, stably expressing non-targeting shRNA (sh-NT, control cells) or sh-CD73 were inoculated into the mammary fat pads of Balb/c mice. The mice were treated with i.p. vehicle or zoledronate (ZOL) each 4th day for total of six times. Additionally, to deplete B-cells, the mice were treated with an anti-CD20 or control IgG antibody. Tumor sizes were assessed with a caliper, TILs were studied with immunostainings. Blood lymphocytes were analyzed with Flow cytometry. Results: Sh-CD73 cells formed significantly smaller tumors, than sh-NT cells. ZOL significantly inhibited the growth of both sh-CD73 and sh-NT tumors, but at sacrifice, this effect of ZOL was more significant against sh-CD73 tumors. ZOL increased the % of CD19+/CD21+ and CD19+/23+ in blood of both mice groups, and this effect was inhibited by anti-CD20 antibody. Although neither treatment alone had an effect, the % of CD3+/CD8+ cells in blood were increased in both mice groups by the combination of ZOL and anti-CD20-antibody. ZOL induced accumulation of B220+, CD4+ and CD8+ TILs into both tumor groups. These TIL effects were reduced with anti-CD20 antibody treatment. Anti-CD20 antibody alone inhibited significantly sh-CD73 tumor growth. Anti-CD20 antibody did not interfere with ZOL inhibition of tumor growth in either group. Conclusions: ZOL has inflammatory effects on blood lymphocytes and TILs, which may be affected by tumor expression of immune system regulating proteins, such as CD73. B cell depletion may further prevent tumor growth, in the context of CD73 inhibition. Further studies are needed to investigate whether B-cell inhibition affects ZOL-induced tumor growth inhibition. Citation Format: Nataliia Petruk, Arafat Siddiqui, Sina Tadayon, Arja Jukkola, Jorma Määttä, Pieta Mattila, Jouko Sandholm, Katri S. Selander. Tumor CD73 regulates zoledronate induced TIL accumulation into triple negative breast cancer. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD2-07.
Abstract P3-05-46: scRNA-seq profiling reveals different tumor immune-microenvironment in triple negative breast cancer and decodes pivotal role of THBS1- SDC1 axis in tumor metastasis
Authors: Liyi Zhang, Qi Zhang, Pei Li, Min Xiong, Yue Zhou, Jingyan Xue, Ming Chen, Wei-Ru Chi, Hengyu Ren, Chih Wan Goh, Douwaner Liu, Liren Wangxu, Yayun Chi, Bingqiu Xiu, Jiong Wu
Journal: Cancer Research (2023)

Abstract ABSTRACT Background: Breast cancer has become the most common cancer worldwide and triple-negative breast cancer (TNBC) is the most aggressive subtype due to the lacks of hormone receptors and HER2 expression. Increasing rate of breast cancer metastasis also need to be solved. Nearly one in four breast cancer patients developed metastasis after treatment, which attributed to 90% cancer related death. Considering highly aggressive pattern of TNBC, TNBC showed higher metastasis probability rather than other subtypes. Therefore, exploring more biomarkers and therapeutic targets are on urgent. Methods: We profiled the transcriptomes of 59646 cells from 12 primary and 4 metastatic tumor samples from Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/). Results: Comparing with primary site, metastatic site was predominated with immunosuppressive tumor microenvironment. In brief, metastatic samples showed increasing numbers of macrophages, lower anti-tumor microenvironment scores, higher malignant cell properties scores, less effective T cells and macrophages, enhanced immune escape potential tumor cells and a later pseudotime state of malignant cells, compared with primary samples. Remarkably, metastatic samples exhibited a stronger interaction of THBS1-SDC1 axis between macrophage subcluster named angiogenesis-1 and malignant cell subcluster named CDKN2A epithelial cells. We subsequently confirmed that higher THBS1-SDC1 expression indicated with poor overall survival and distant metastatic free survival of TNBC patients in The Cancer Genome Atlas (TCGA) TNBC cohort. Conclusion: Our immune landscape of TNBC ecosystem provide deeper insights into tumor metastasis and offer potential biomarkers and therapeutic target for TNBC. Key words: Breast cancer; immune-microenvironment; THBS1; SDC1; metastasis Citation Format: Liyi Zhang, Qi Zhang, Pei Li, Min Xiong, Yue Zhou, Jingyan Xue, Ming Chen, Wei-Ru Chi, Hengyu Ren, Chih Wan Goh, Douwaner Liu, Liren Wangxu, Yayun Chi, Bingqiu Xiu, Jiong Wu. scRNA-seq profiling reveals different tumor immune-microenvironment in triple negative breast cancer and decodes pivotal role of THBS1- SDC1 axis in tumor metastasis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-46.
Abstract P3-05-49: Number of involved organs at baseline is prognostic for overall survival in patients with metastatic breast cancer: Results from the AGMT_MBC-Registry
Authors: Gabriel Rinnerthaler, Simon P. Gampenrieder, Christoph Tinchon, Andreas Petzer, Marija Balic, Sonja Heibl, Margit Sandholzer, August F. Zabernigg, Daniel Egle, Christopher Hager, Petra Pichler, Florian Roitner, Johannes Andel, Kathrin Strasser-Weippl, Michael Knauer, Michael Hubalek, Christian F. Singer, Richard Greil
Journal: Cancer Research (2023)

Abstract Background: Hormone-receptor (HR) status, HER2 Status, de novo metastatic disease, distant recurrence-free interval (DRFI), and visceral disease are known prognostic factors in metastatic breast cancer (MBC). Therefore, in the majority of clinical trials, randomization is stratified for these parameters. Whether the number of involved organs at baseline has an additional prognostic value was examined in this analysis. Patients and methods: The AGMT-MBC-Registry is a multicenter nationwide ongoing retrospective and prospective registry for MBC patients in Austria. In this analysis, patients with known HR status, HER2 status, and available survival data were included. Multivariable hazard ratios were estimated by COX proportional hazard models. For variable selection a backward stepwise model selection using the Akaike information criterion was performed. Results: As of 04/05/2022, 2,235 patients have been included in the registry, of which 1,840 patients fulfilled the inclusion criteria. In two different multivariable COX proportional hazard models for overall survival, the number of involved organs was a highly statistically significant independent prognostic factor: (1) a model including the number of involved organs at baseline together with known prognostic factors (see Table 1); (2) a stepwise selection model additionally including menopausal status and involved metastatic organ sites (bone, liver, lung, brain, and lymph nodes) separately. This effect was maintained in sensitivity analysis taking different breast cancer subtypes as well as visceral and non-visceral disease into account. Conclusion: The number of involved organs at baseline is an independent prognostic factor in MBC and should be considered as a stratification factor in randomized trials. Table 1. Multivariable Model for overall survival. Citation Format: Gabriel Rinnerthaler, Simon P. Gampenrieder, Christoph Tinchon, Andreas Petzer, Marija Balic, Sonja Heibl, Margit Sandholzer, August F. Zabernigg, Daniel Egle, Christopher Hager, Petra Pichler, Florian Roitner, Johannes Andel, Kathrin Strasser-Weippl, Michael Knauer, Michael Hubalek, Christian F. Singer, Richard Greil. Number of involved organs at baseline is prognostic for overall survival in patients with metastatic breast cancer: Results from the AGMT_MBC-Registry [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-49.
Abstract P6-04-07: Primary Diagnosis of Breast Biopsies supported by AI versus Microscope: Multi-Site Clinical Reader Study
Authors: Anne Salomon, Alona Nudelman, Joanna Cyrta, Marina Maklakovski, Anat Albrecht Shach, Geraldine Sebag, Giuseppe Mallel, Ira Krasnitsky, Tali Feinberg, Manuela Vecsler, Judith Sandbank
Journal: Cancer Research (2023)

Abstract Objective This study aimed to clinically validate the use of an AI-based solution by pathologists for the primary diagnosis of breast core needle biopsies as compared with the gold standard practice (review on the microscope). Methods A two-arm prospective reader study comparing the performance of pathologists using an AI-based solution with pathologists using a microscope was performed at two sites (different staining and digital scanners). Both arms were compared to ground truth (GT) established by the consensus of two breast pathologists. Rates of major discrepancies between each arm and GT, as determined by an adjudicating pathologist, were compared. Results Eight pathologists participated in the study and reported on 385 cases (442 HES and 330 H&amp;E slides), each case being reported twice, once in each study arm. Pathologists first reviewed only H&amp;E/HES slides, if requested and available, they were provided with IHCs, while the AI results were on H&amp;E/HES only. The major discrepancy rates of the microscope arm and of the AI arm against GT were 4.42% and 3.12%, respectively, demonstrating a 29.4% reduction in major discrepancies. Pathologists with AI demonstrated very high accuracy for the detection of invasive carcinoma with sensitivity and specificity of 100% for both, as well as for DCIS/ADH with sensitivity of 92.4% and specificity of 97.8%. Conclusions This multi-site reader study reports diagnostic accuracy improvements by pathologists performing diagnosis and reporting with the support of a first read AI solution for breast biopsies. The AI solution performed accurately and generalized well for different staining platforms and different scanners. Thus, AI solutions could be used as significant aiding tools for pathologists in clinical decision-making in routine pathology practice, enhancing the quality and reproducibility of diagnosis. Citation Format: Anne Salomon, Alona Nudelman, Joanna Cyrta, Marina Maklakovski, Anat Albrecht Shach, Geraldine Sebag, Giuseppe Mallel, Ira Krasnitsky, Tali Feinberg, Manuela Vecsler, Judith Sandbank. Primary Diagnosis of Breast Biopsies supported by AI versus Microscope: Multi-Site Clinical Reader Study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-04-07.